Association of anticoagulation dose and survival in hospitalized COVID‐19 patients: A retrospective propensity score‐weighted analysis

Abstract

Background Hypercoagulability may contribute to COVID‐19 pathogenicity. The role of anticoagulation (AC) at therapeutic (tAC) or prophylactic doses (pAC) is unclear. Objectives We evaluated the impact on survival of different AC doses in COVID‐19 patients. Methods Retrospective, multi‐center cohort study of consecutive COVID‐19 patients hospitalized between March 13 and May 5, 2020. Results A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n = 642) required intensive care unit (ICU) stay. 60.9% received pAC (n = 2121), 28.7% received ≥3 days of tAC (n = 998), and 10.4% (n = 361) received no AC. Propensity score (PS) weighted Kaplan‐Meier plot demonstrated different 25‐day survival probability in the tAC and pAC groups (57.5% vs 50.7%). In a PS–weighted multivariate proportional hazards model, AC was associated with reduced risk of death at prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22‐0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05‐0.23]) compared to no AC. Major bleeding occurred more frequently in tAC patients (81 [8.1%]) compared to no AC (20 [5.5%]) or pAC (46 [2.2%]) subjects. Conclusions Higher doses of AC were associated with lower mortality in hospitalized COVID‐19 patients. Prospective evaluation of efficacy and risk of AC in COVID‐19 is warranted.

Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study

“…Data were censored at 35 days of follow up in n=430 (10.0%) patients with a follow up longer than 35 days.…”

“…However, Pesavento et al (34) showed in a smaller cohort of Italian patients that the rate of relevant bleeding was higher in patients treated with (sub)therapeutic doses of anticoagulants, while overall mortality tended to be higher as compared to patients treated with standard prophylactic doses. Other observational studies reported that treatment with a therapeutic/higher dosage of anti-coagulant drugs was associated with a higher incidence of bleeding, despite a decrease of in-hospital mortality (7,35). HIT is a severe immune-mediated complication of heparin therapy, leading to platelet activation, platelet consumption, and thrombin generation.…”

COVID-19 and thrombosis: From bench to bedside

“…Because of the high risk of thromboembolic complications and heparin's unique pharmacology demonstrating a reduction in both inflammation and coagulation markers in COVID-19, heparins are being studied for additional clinical endpoints of reduction in hospitalizations, progression to non-invasive mechanical ventilation, as well as mortality. Some, but not all, recently reported retrospective cohort studies, suggest an in-hospital mortality benefit for both UFH and LMWH administered at both prophylaxis and therapeutic treatment doses, especially in patients with more severe COVID-19 as evidenced by elevated D-dimer or need for mechanical ventilation [ 76 , [96] , [97] , [98] , [99] , [100] , [101] , [102] , [103] ] (Summarized in Table 2 ).…”

“…In the few studies that have reported the frequency of major bleeding, results are mixed with two studies reporting no difference in major bleeding between therapeutic anticoagulation and prophylactic anticoagulation and one study reporting an increased risk of major bleeding [ 96 , 98 , 99 , 101 ]. Because the data reported in these studies are limited with some lacking details regarding heparin type, dose, the reason treatment versus prophylaxis dosing was selected, as well as the potential for confounding, randomized prospective trials are needed.…”

Characteristics and outcomes in hospitalized COVID-19 patients during the first 28 days of the spring and autumn pandemic waves in Milan: An observational prospective study

“…Less advanced disease stages, a lower number of patients with severe aRF at admission and an increased proportion of patients treated with anticoagulant therapy may have thus contributed to decreased mortality [ 14 , 15 ]. In fact, PaO2/FiO2<200 mmHg [ 10 ] and D-dimer >2.000 FEU [ 12 ] were demonstrated to be independent risk factors for adverse outcomes, while the increased use of systemic corticosteroids [ 6 , 7 , 14 ] and anticoagulation [ 13 , 14 ] showed a reduction in mortality in patients with severe COVID-19 pneumonia.…”